Reference value methodology

The first-principles calculation of NIS spectra has several important aspects. First of all, they greatly assist the assignment of NIS spectra. Secondly, the elucidation of the vibrational frequencies and normal mode compositions by means of quantum chemical calculations allows for the interpretation of the observed NIS patterns in terms of geometric and electronic structure and consequently provide a means of critically testing proposals for species of unknown structure. The first-principles calculation also provides an unambiguous way to perform consistent quantitative parameterization of experimental NIS data. Finally, there is another methodological aspect concerning the accuracy of the quantum chemically calculated force fields. Such calculations typically use only the experimental frequencies as reference values. However, apart from the frequencies, NIS probes the shapes of the normal modes for which the iron composition factors are a direct quantitative measure. Thus, by comparison with experimental data, one can assess the quality of the calculated normal mode compositions. 

It is also noted that there is overlap in the individual UFs and that the application of five UFs of ten for the chronic reference value (yielding a total UF of 100,000) is inappropriate. In fact, in cases where maximum uncertainty exists in all five areas, it is unlikely that the database is sufficient to derive a reference value. Uncertainty in four areas may also indicate that the database is insufficient to derive a reference value. In the case of the RfC, the maximum UF would be 3,000, whereas the maximum would be 10,000 for the RfD. This is because the derivation of RfCs and RfDs has evolved somewhat differently. The RfC methodology (US-EPA 1994) recommends dividing the interspecies UF in half, one-half (10° ) each for toxicokinetic and toxicodynamic considerations, and it includes a Dosimetric Adjustment Factor (D AF, represents a multiplicative factor used to adjust an observed exposure concentration in a particular laboratory species to an exposure concentration for humans that would be associated with the same delivered dose) to account for toxicokinetic differences in calculating the Human Equivalent Concentration (HEC), thus reducing the interspecies UF to 3 for toxicodynamic issues. RfDs, however, do not incorporate a DAF for deriving a Human Equivalent Dose (HED), and the interspecies UF of 10 is typically applied, see also Section 5.3.4. It is recommended to limit the total UF applied for any particular chemical to no more than 3000, for both RfDs and RfCs, and avoiding the derivation of a reference value that involves application of the full 10-fold UF in four or more areas of extrapolation. 

The overlap of areas covered by the FQPA factor and those addressed by the traditional UFs was recognized, and it was concluded that the current UFs, if appropriately applied using the approaches recommended in the review (i.e., US-EPA 2002), will be adequate in most cases to cover concerns and uncertainties regarding the potential for pre- and postnatal toxicity and the completeness of the toxicology database. In other words, an additional UF is not needed in the RfC/RfD methodology because the currently available factors are considered sufficient to account for uncertainties in the database from which the reference values are derived (and it does not exclude the possibility that these UFs may be decreased or increased from the default value of 10). 

For the interpretation of monitoring results in general two approaches might be used (i) the comparison with a reference values obtained from representative studies and (ii) a risk assessment methodology related to the hazard of the compound. The latter results in guideline values. 

The reference concentration (RfC) methodology to estimate benchmark values for noncancer toxicity of inhaled chemicals was adapted for inhalation studies from the reference dose methodology used for oral exposure assessment. The same general principles were used, but the RfC methodology was expanded to account for the dynamics of the respiratory system as a portal of entry. The reference dose (RfD) methodology included dosimetric adjustments to account for species-specific relationships of exposure concentrations to deposited or delivered doses. Particles and gases are treated separately, and the type of toxicity observed influences the dosimetric adjustment applied to score the exposure concentration for animals to a human equivalent concentration. 

In this section, methodological principles and reference values are given for several of the methods used to measure red cell enzymes. Methodological details of these methods are given in the Evolve site that accompanies this book at http //evolve.elsevier. com/Tietz/textbook. 

Because of methodological differences, reference values for folate are method dependent. The data collected from the NHANES of 1988 to 1994 in the United States, in which almost 3000 blood samples were analyzed, produced reference intervals of 2.6 to 12.2 xg/L (6.0 to 28.0nmol/L) for serum folate and 103 to 411)Lig/L (237 to 945nmol/L) for... 

The reference values used for our studies were drawn in part on the basis of data available in the literature and in part from our own experimental data. The literature does not provide homogeneous data, given the variety of research aims and methodological approaches. However, precisely for this reason, we can consider them because of the large number of environmental variables (Table 11.6). 

Reference values were derived from 30 premature infants (<36 weeks of gestation), 34 term newborns (>36 weeks of gestation), 13 children younger than 5 years, 20 children older than 5 years, and 9 control adults. All control subjects were healthy with no evidence of severe systemic or especially metabolic disease. The compounds are listed in the order of their chromatographic appearance, i.e. in the order of their MUs (DBS 30 mxO.25 mm I.D. fused-silica capillary column, film thickness 1 pm, J W, Rancho Cordova, CA, USA). For a detailed description of the methodology see ref. (18). Abbreviations employed were Min.=minimal, and Max.=maximal values, n.d. = not detectable (<1 mmol/mol of creatinine), - = undetermined. 

Enzymatic method. Reference values vary with the methodology. 

Detailed use of the proposed methodology for calculating the deformation parameters of a sample of cesium nanoparticles is discussed below. The number of atoms in nanoparticles ranged from 216 to 200,190. Diameter equilibrium nanoparticles with cesium is from 3 nm to 27 nm. The number of atoms is increased as long as the elastic modulus reaches a value nanoparticles reference value Cs. An important task in the development of nanotechnology in Russia and abroad is to determine the size of the nanoparticles, in which the mechanical characteristics will be the same as the reference values of the macro stuff. Of particular interest to the study of mechanical characteristics of the nanoparticles are small size nanostructures with the number of atoms of <10,000. 

Particularly in Food Microbiology, the results of the assessment of a particular property of a food depend greatly on the method used for its determination. Therefore Reference Values carry little weight unless the method for assessing compliance is exactly specified. Hence methodology forms an essential part of Reference Values. Consequently techniques with enormous variability and high margin of error should be abandoned. 

The protocol was tested on the AE6 and BH6 test sets (6 atomization energies and 6 barrier heights ) and for further 26 atomization energies from the G2/97 test set for which values from the original W4 protocol were available. The computational savings due to the use of the F12 methodology made possible the application to the entire G2/97 set. The new computed values for this test set are expected to be more reliable than the experimental ones and the authors recommend to use these as reference values for the assessment of more approximate methods. ... 

As usually viewed by the reference material producers, a fundamental philosophy of certification rests on the concept of independent methodology, which is the application of theoretically and experimentally different measurement techniques and procedures to generate concordant results leading to one reliable assigned value for the property. Such assigned values are thus method-independent. Extractable concentrations are generated by specific procedures and are thus method-dependent, an idea that has to be rationalized with the fundamental method-independent concept in reference material certification work. 

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